The present invention relates generally to the preparation of ketones. More particularly, this invention relates to a method and apparatus for preparing ketones via catalytic reaction from an aldehyde and a carboxylic acid.
In general, unsymmetrical ketones are useful as intermediates for the production of numerous specialty chemicals. More specifically, methyl cyclopropyl ketone (MCPK) has a variety of current and potential uses including, among others, the production of specialty agricultural and pharmaceutical compounds.
Numerous literature references cite and disclose various well-known processes for the preparation of ketones. These processes include oxidation of secondary alcohols, Friedel-Crafts acylation, reaction of acid chlorides with organo cadmium compounds, acetoacetic ester synthesis and decarboxylation from acids, among others.
Text and literature references also detail problems associated with using these processes to produce ketones. These include problems such as the unavailability and/or cost of raw materials, the requirement of multi-stage processing, the low conversion of the raw materials and/or the low selectivity of the desired ketones, and the production of corrosive or hard to separate products.
Ketone production processes have also been described in the patent literature. For example, U.S. Pat. Nos. 4,528,400 and 4,570,021 disclose a process for the preparation of unsymmetrical ketones by a catalytic vapor phase reaction using reactants such as ketones with carboxylic acids. However, laboratory trials using acetone and cyclopropanecarboxylic acid resulted in the production of high quantities of gamma-butyrolactone, several pentenones and pentanones, but no MCPK.
U.S. Pat. Nos. 3,410,909 and 3,453,331 disclose processes for the preparation of symmetrical and unsymmetrical ketones from aldehydes containing up to 8 carbons in a non-cyclic saturated aliphatic chain.
German Patent Disclosure No. P36 37 788.0 (1986) discloses a specific condensation reactor process for the preparation of methyl cyclopropyl ketone (MCPK) from cyclopropanecarboxylic acid or its derivatives. However, although examples from this patent show raw material conversion of from 58 to 99 percent and selectivity to MCPK of 42 to 75 percent, the liquid hourly space velocity (LHSV) or weight hourly space velocity (WHSV) values of less than 1 (i.e., 0.25 to 0.99) minimize the industrial usefulness of this condensation reactor process.
European Patent Application No. 0 085 996 also discloses processes for the preparation of unsymmetric aliphatic ketones at atmospheric pressures (or slightly above) and at relatively low WHSV.
U.S. Pat. No. 3,966,822 (Fukui et al.) discloses the preparation of ketones from aldehydes in the presence of zirconium oxide and various other catalysts. U.S. Pat. No. 3,466,334 (Young et al.) discloses synthesis of ketones from an aldehyde and an acid in the presence of a catalyst comprised of an alumina-supported oxidized form of lithium. U.S. Pat. No. 3,453,331 (Hargis et al.) discloses a process for the synthesis of ketones from aldehydes using various alumina-supported oxidized forms of various metals. WO 00/30448, published Jun. 2, 2000 and entitled xe2x80x9cMethod and Apparatus for the Preparation of Ketonesxe2x80x9d, describes methods for the catalyst-mediated production of ketones. In general, an acid or aldehyde or derivatives thereof and a carboxylic acid are reacted in the presence of a catalyst to produce a desired ketone.
The most common industrial processes for the production of ketones typically involve the reaction of an acid in the presence of a catalyst. Catalyzed reactions such as these can be low in yield due to side reactions and/or the reactant throughput can be low due to system requirements.
Thus, there is a need in the art for a method to produce ketones in high yields in a cost-effective manner.
The present invention relates to a method and an apparatus for producing ketones via a one step synthesis from aldehydes. This synthesis has good selectivity and conversion rates. Particularly desirable reaction products include asymmetrical ketones such as methyl cyclopropyl ketone (MCPK). The method and apparatus of the present invention utilizes readily available and relatively inexpensive raw materials and results in high conversion and selectivity rates.
Generally, the raw materials used in this invention include an aldehyde, a carboxylic acid, and a source of oxygen, such as water.
In a preferred embodiment, this invention involves the reaction of cyclopropanecarboxaldehyde, acetic acid, and water at elevated temperatures in the presence of a catalyst to form methyl cyclopropyl ketone (MCPK). Vaporized reactants flow through a tube reactor provided with a suitable catalyst.
In one aspect, this invention is a method for the production of a ketone comprising providing a tube reactor having a catalytic bed; providing a carboxylic acid, a source of oxygen; and an aldehyde, and passing the carboxylic acid, the source of oxygen, and the aldehyde, each in a vapor phase, through the catalytic bed at a weight hourly space velocity greater than 1 to form the ketone. The ketone may be an asymmetrical ketone and the carboxylic acid and the aldehyde may be heated before entering the tube reactor. Preferably, the weight hourly space velocity is in the range of 1 to 20. In a preferred embodiment, the weight hourly space velocity is in the range of 2 to 20. In another preferred embodiment, the weight hourly space velocity is in the range of 5 to 20. The reacting may take place in two or more tube reactors connected in parallel. Preferably, the catalyst is a theoretical monolayer on a solid support. The method may also include the step of recovering the ketone. In preferred embodiments, the source of oxygen is water. In another preferred embodiment, the ketone is methyl cyclopropyl ketone, the aldehyde is cyclopropanecarboxaldehyde, and the acid is acetic acid. The weight ratio of the carboxylic acid: source of oxygen: aldehyde may range from 1:1:1 to 20:1:1. The catalyst may be selected from MgO, TiO2, ZrO2, ZnO, CeO2, and Ce2O3. A preferred catalyst is CeO2 on a TiO2 support wherein there is about 15 to 20% CeO2 per gram of TiO2. The method may be a continuous process.
In a second aspect, this invention is a method of preparing a ketone comprising providing a plurality of tube reactors, each having a catalytic bed; providing a raw material feed comprised of a carboxylic acid, a source of oxygen, and an aldehyde, to produce the ketone; selectively passing the raw material feed through the catalytic bed of at least one of the plurality of tube reactors at a temperature of between about 350xc2x0 C. and 500xc2x0 C. and a weight hourly space velocity of greater than 1; and recovering the ketone. This method may also include selectively stopping the passage of raw material feed through the catalytic bed of the at least one tube reactor and passing the raw material feed through the catalytic bed of at least one of the plurality of tube reactors, and/or regenerating the catalytic bed of the at least one tube reactor through which the passage of raw material feed has been stopped. Preferably, the catalytic bed includes a CeO2/TiO2 catalyst structure having about 15 to 20% CeO2 per gram of TiO2.
In a third aspect, this invention is a process for the production of a ketone comprising reacting acetic acid with cyclopropanecarboxaldehyde and with water to form methyl cyclopropyl ketone; wherein the reacting occurs in the vapor phase and in the presence of a catalyst.
In a fourth aspect, this invention is a process for the preparation of a compound of formula (I) 
wherein:
R1 is cycloalkyl having from three to six ring carbon atoms which is unsubstituted or which has one or more substituents selected from the group consisting of R4 and halogen; R2 is halogen; straight- or branched-chain alkyl having up to six carbon atoms which is substituted by one or more xe2x80x94OR5; cycloalkyl having from three to six carbon atoms; or a member selected from the group consisting of nitro, cyano, xe2x80x94CO2R5, xe2x80x94NR5R6, xe2x80x94S(O)pR7, xe2x80x94O(CH2)mOR5, xe2x80x94COR5, xe2x80x94N(R8) SO2R7, xe2x80x94OR7, xe2x80x94OH, xe2x80x94OSO2R7, xe2x80x94(CR9R10)tSOqR7a, xe2x80x94CONR5R6, xe2x80x94N(R8)xe2x80x94C(Z)Y, xe2x80x94(CR9R10)NR8R11 and R4; n is zero or an integer from one to three; when n is greater than one, then the groups R2 are the same or different; m is one, two or three; p is zero, one or two; q is zero, one or two; t is an integer from one to four; R3 is straight- or branched-chain alkyl group containing up to six carbon atoms which is unsubstituted or which has one or more substituents selected from the group consisting of halogen, xe2x80x94OR, xe2x80x94CO2R5, xe2x80x94S(O)pR7, phenyl or cyano; or phenyl which is unsubstituted or which has one or more substituents selected from the group consisting of halogen, xe2x80x94OR5 and R4; R4 is straight- or branched-chain alkyl, alkenyl or alkynyl having up to six carbon atoms which is unsubstituted or is substituted by one or more halogen; R5 and R6, which are the same or different, are each hydrogen or R4; R7 and R7a independently are R4, cycloalkyl having from three to six ring carbon atoms, or xe2x80x94(CH2)w-phenyl wherein phenyl is unsubstituted or is substituted by from one to five R12 which are the same or different; w is zero or one; R8 is hydrogen; straight- or branched-chain alkyl, alkenyl or alkynyl having up to ten carbon atoms which is unsubstituted or is substituted by one or more halogen; cycloalkyl having from three to six ring carbon atoms; xe2x80x94(CH2)w-phenyl wherein phenyl is unsubstituted or is substituted by from one to five R12 which are the same or different; or xe2x80x94OR13; R9 and R10 independently are hydrogen or straight- or branched-chain alkyl having up to six carbon atoms which is unsubstituted or is substituted by one or more halogen; R11 is xe2x80x94S(O)qR7 or xe2x80x94C(Z)Y; R12 is halogen; straight- or branched-chain alkyl having up to three carbon atoms which is unsubstituted or is substituted by one or more halogen; or a member selected from the group consisting of nitro, cyano, xe2x80x94S(O)pR3 and xe2x80x94OR5; Y is oxygen or sulfur; Z is R4, xe2x80x94NR8R13, xe2x80x94NR8NR13R14,xe2x80x94SR7 or xe2x80x94OR7; and R13 and R14 independently are R8, or an agriculturally acceptable salt or metal complex thereof,
which process comprises:
(i) reacting a compound of formula (II) 
xe2x80x83wherein R15 is a straight- or branched-chain alkyl group having up to six carbon atoms with a compound of formula (III) 
xe2x80x83in an aprotic solvent in the absence of a base to form a compound of formula (IV) 
(ii) reacting a compound of formula (IV) with a compound that contains a leaving group L [such as alkoxy or N,N-dialkylamino, esp. ethoxy and CH(OCH2CH3)3] to form a compound of formula (V) 
(iii) reacting a compound of formula (V) with hydroxylamine or a salt of hydroxylamine to form a compound of formula (I), wherein the process further comprises producing the compound of formula (III) by providing a catalytic bed; providing a raw material feed comprising a carboxylic acid, water, and R1COH in the ratio of from 1:1:1 to 20:1: 1; passing the raw material feed through the catalytic bed at a temperature of between about 350xc2x0 C. and 500xc2x0 C. at a weight hourly space velocity greater than one; and separating the compound of formula (III).
Preferably, the carboxylic acid is acetic acid. In a fifth aspect, this invention is the method for the preparation of a compound of formula (X) 
comprising:
(i) reacting a compound of formula (XI) 
xe2x80x83with a compound of formula (XII) 
xe2x80x83to form a compound of formula (XIII) 
(ii) reacting a compound of formula (XIII) with CH(OCH2CH3)3 to form a compound of formula (XIV) 
(iii) reacting a compound of formula (XIV) with hydroxylamine or a salt of hydroxylamine to form a compound of the formula (XV) 
(iv) reacting a compound of formula (XV) with chloroperbenzoic acid to form a compound of the formula (X), wherein the process further comprises producing the compound of formula (XII) by providing a catalytic bed; providing a raw material feed comprised of a carboxylic acid, water, and R1COH in the ratio of from 1:1:1 to 20:1:1; passing the raw material feed through the catalytic bed at a temperature of between about 350xc2x0 C. and 500xc2x0 C. at a weight hourly space velocity greater than one; and separating the compound of formula (XII).